Perhaps the most fundamental variation is one of age. The average
age of the women in the WHI study was 63 with a range of 50-79 and 22%
being recruited for therapy over the age of 70. The study demonstrated
an increase in breast cancer and VTE, a decrease in colon cancer and
fractures of the hip and spine as well as an unexpected increase in heart
attacks and stroke. (1) However it should be recognised that as 97% of
patients in normal clinical practice commence treatment below the age
of 60 and it is this age cohort of patients which is of particular interest
to the prescribing physician. (11) The data from this age group
are reassuring, as a later report the WHI study in 2003 showed that the
excess of cardiovascular events (12) occurred only in women starting
oestrogen and progestogen therapy 20 years after the menopause, and that
there was a non significant (HR 0.89) decrease in these events in women
starting the therapy within 10 years of the menopause.

Similarly the oestrogen only-arm, (13) which was reportedly stopped
in 2004 because of an excess of stroke, showed that in the 50-59 year
old age group there was a 42% decrease in coronary heart disease being
much the same as the protection found in the former case control studies.
There was also a 28% decrease in breast cancer, a 41% decrease in colo-rectal
cancer, a 27% decrease in deaths and a 20% decrease in global index pathology. The
8% increase in stroke was in fact 19 patients in the control group and
19 patients in the active group. None of the considerable beneficial
changes were significant but it does raise a question why this age cohort
of the oestrogen- only study was stopped as results could have confirmed
the cardiovascular and colo-rectal benefits in the many earlier observational
studies. It was a lost opportunity to solve this continuing controversy.